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Open Access Research article

Monoallelic deletion of the microRNA biogenesis gene Dgcr8 produces deficits in the development of excitatory synaptic transmission in the prefrontal cortex

Claude M Schofield12, Ruby Hsu12, Alison J Barker12, Caitlyn C Gertz12, Robert Blelloch3 and Erik M Ullian12*

Author Affiliations

1 Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94143, USA

2 Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA

3 Department of Urology, University of California, San Francisco, San Francisco, CA 94143, USA

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Neural Development 2011, 6:11  doi:10.1186/1749-8104-6-11

Published: 5 April 2011

Abstract

Background

Neuronal phenotypes associated with hemizygosity of individual genes within the 22q11.2 deletion syndrome locus hold potential towards understanding the pathogenesis of schizophrenia and autism. Included among these genes is Dgcr8, which encodes an RNA-binding protein required for microRNA biogenesis. Dgcr8 haploinsufficient mice (Dgcr8+/-) have reduced expression of microRNAs in brain and display cognitive deficits, but how microRNA deficiency affects the development and function of neurons in the cerebral cortex is not fully understood.

Results

In this study, we show that Dgcr8+/- mice display reduced expression of a subset of microRNAs in the prefrontal cortex, a deficit that emerges over postnatal development. Layer V pyramidal neurons in the medial prefrontal cortex of Dgcr8+/- mice have altered electrical properties, decreased complexity of basal dendrites, and reduced excitatory synaptic transmission.

Conclusions

These findings demonstrate that precise microRNA expression is critical for the postnatal development of prefrontal cortical circuitry. Similar defects in neuronal maturation resulting from microRNA deficiency could represent endophenotypes of certain neuropsychiatric diseases of developmental onset.